Injectable Functional Porous Carbon-Loaded Hydrogel with Long-Term Retention and Synergistic Anti-Tumor Properties for Tumor Therapy.

In situ therapies show significant promise for the treatment of unresectable tumors that lack tumor supply vessels. However, it remains a tremendous challenge to achieve precise delivery and sustained release of anti-tumor agents with synergistic anti-tumor efficacy. Here, a novel in situ injectable hydrogel (denoted as CFe/βCP+Cis hydrogel) has been designed by integrating β-CD-g-PEGMA (βCP) molecular brush hydrogel with functional carbon nanozyme (CFe) and cisplatin. The reversible gel network of βCP hydrogel and the rigid nanoscale architecture of CFe endow CFe/βCP+Cis hydrogel with properties conducive to injectability and long-term retention (more than 63 days). CFe and cisplatin mixed in hydrogel are both gradually released into the tumor tissue, facilitating the synergistic anti-tumor efficacy via ferroptosis and cytotoxicity. In addition, CFe/βCP hydrogel can reduce the M2-like/M1-like ratio of macrophages and promote the infiltration of CD8 T cells in the tumor microenvironment to enhance anti-tumor immunity. As a result, the CFe/βCP+Cis hydrogel demonstrates significant potential for precise and sustained tumor treatment through chemodynamic therapy, chemotherapy, immunoregulation, and long-term retention properties.